Endocrinologic and Metabolic Drugs Advisory Committee Meeting

June 10, 2003

Addendum to the FDA Briefing Document

Data listings for patients in the final height populations of Studies GDCH and E001

 

The data on the following pages are sorted by study and by treatment. The variables included in each table are the following:

PATIENT = patient randomization number

STIMTEST = stimulation test used to determine trial eligibility; note that most GDCH patients were given more than one test and the test recorded here is the one producing the peak growth hormone concentration

STIMGH = peak growth hormone concentration measured prior to randomization

SEX = F: female M: male

BLTAN = baseline tanner stage; in E001 all patients were at Stage 1

AGE = baseline age

BAGE = baseline Greulich-Pyle bone age

BLHV = height velocity in inches measured prior to treatment

PH = baseline predicted height in inches

TARGET= target height in inches (this is missing for a few patients without parent information)

BASEIGF = baseline IGF-1, this baseline was calculated by the sponsor from all IGF-1 data available prior to randomization; for some patients, multiple measurements were made on consecutive days or over a several year time period. The units of measurment for Study GDCH are ng/ml and for Study E001, mU/L. Values out of the normal range for Study GDCH are highlighted in the table; note all values were low. No ranges were provided in the database for Study E001. The normal limits for GDCH patients is presented on the last page.

FINALIGF = the last IGF-1 value measured while on treatment; post-randomization values were only available for Study GDCH

YEARS = the total number of years of randomized treatment

FINHT = final height in inches

DIFFHTPH= final height minus predicted height inches

Study E001 Final Height Population Data

--------------------------------------- THERAPY=Dose 1 ----------------------------------------

s d

P t b i

A i s t a f

T m t b a s Y f f

I t i l b b r e E i h

E e m s t A a l g i A n t

N s g e a G g h p e g R h p

T t h x n E e v h t f S t h

3016 Glucagon 26.00 F 1 8.7 7.3126 2.25 56.41 59.48 . 7.42 57.72 1.31

4002 . F 1 8.2 5.5453 1.87 . 61.43 64.00 7.10 59.36 .

6004 Arginine I 24.00 M 1 6.7 5.5105 2.52 . 68.25 32.00 9.61 67.47 .

6007 Arginine I 24.00 M 1 12.2 12.0940 1.41 58.04 69.81 51.00 6.78 61.74 3.69

6010 L-dopa 26.00 M 1 12.4 9.9559 1.37 63.04 65.33 91.00 5.81 64.86 1.82

6014 Arginine I 22.00 F 1 8.5 6.5721 2.37 58.72 64.35 62.00 7.72 59.79 1.06

6017 Arginine I 21.00 M 1 12.7 10.4631 1.96 63.75 66.11 86.00 4.19 66.07 2.32

6019 Arginine I 20.40 M 1 15.2 11.0498 1.32 67.24 66.46 134.00 5.04 67.08 -0.16

6021 Arginine I 21.40 M 1 13.0 9.4188 1.68 66.69 65.52 64.00 5.04 67.35 0.66

6022 Clonidine 30.00 M 1 9.4 6.5547 2.46 63.77 65.52 37.00 8.89 65.64 1.87

6025 Clonidine 45.00 F 1 10.8 9.9191 2.88 58.14 61.23 134.00 0.27 60.33 2.19

6030 Arginine I 40.00 F 1 9.4 . 2.45 . 66.11 107.00 3.33 60.22 .

7002 Insulin St 30.00 M 1 10.1 9.0210 1.31 58.50 66.79 129.00 7.53 62.71 4.21

7008 . M 1 11.7 9.2398 1.08 60.93 64.06 52.00 5.49 62.87 1.94

7014 . M 1 9.9 8.7625 1.73 61.30 66.11 69.00 8.70 64.94 3.63

7017 . F 1 7.0 5.2886 1.39 . 55.77 80.00 7.06 55.22 .

7020 . M 1 11.0 8.7426 1.15 64.35 63.08 94.00 6.96 66.96 2.62

 

 

Final ht minus Predicted ht (inches)

Mean 2.09

Median 1.94

 

Study E001 Final Height Population Data

--------------------------------------- THERAPY=Dose 2 ----------------------------------------

s d

P t b i

A i s t a f

T m t b a s Y f f

I t i l b b r e E i h

E e m s t A a l g i A n t

N s g e a G g h p e g R h p

T t h x n E e v h t f S t h

1023 Insulin St 10.83 M 1 12.4 7.4000 1.55 . 67.74 112.00 5.97 67.78 .

4006 Arginine I 25.40 F 1 10.5 7.2929 1.10 59.02 63.06 44.00 6.87 65.13 6.11

4033 . M 1 8.9 8.2951 2.00 61.23 67.86 114.00 8.49 63.38 2.14

6003 Arginine I 33.00 F 1 11.4 9.3859 3.01 56.75 63.57 98.00 5.32 59.28 2.53

6005 L-dopa 18.00 F 1 6.0 5.7527 . . 59.87 68.00 12.15 58.66 .

6008 Arginine I 37.00 M 1 10.1 8.3647 1.53 60.38 67.08 210.00 7.23 61.39 1.01

6011 Arginine I 27.00 M 1 12.1 9.2398 1.72 64.51 66.89 80.00 5.84 68.25 3.74

6016 L-dopa 93.00 F 1 6.3 3.3437 4.11 . 63.30 66.00 7.84 57.72 .

6023 Clonidine 20.00 F 1 12.5 10.0277 2.47 59.02 62.60 77.00 2.53 62.52 3.50

6028 Clonidine 20.00 M 1 12.5 10.4332 2.18 62.95 68.64 114.00 5.00 64.97 2.02

6032 Arginine I 17.00 M 1 9.8 8.2652 2.03 63.43 65.99 218.00 7.53 66.53 3.10

6033 Arginine I 24.70 M 1 12.4 11.7559 2.40 63.11 70.01 . 4.99 62.63 -0.47

6035 L-dopa 75.00 M 1 12.4 10.7813 1.90 63.34 73.91 . 7.48 64.94 1.60

7003 Insulin St 26.80 F 1 10.3 10.0277 1.61 55.56 57.37 191.00 4.23 58.66 3.09

7009 . F 1 9.7 9.5636 0.92 53.92 59.28 100.00 6.00 57.72 3.80

7018 . M 1 8.8 6.4353 1.51 66.27 63.38 93.00 9.03 67.86 1.59

 

 

Final ht minus Predicted ht (inches)

Mean 2.60

Median 2.53

 

Study E001 Final Height Population Data

--------------------------------------- THERAPY=Dose 3 ----------------------------------------

s d

P t b i

A i s t a f

T m t b a s Y f f

I t i l b b r e E i h

E e m s t A a l g i A n t

N s g e a G g h p e g R h p

T t h x n E e v h t f S t h

3012 Arginine I 22.10 F 1 9.9 6.7696 1.62 62.03 60.26 . 8.41 63.18 1.15

4005 Insulin St 27.00 M 1 12.4 8.3945 1.35 . 64.16 57.00 7.03 66.04 .

6001 Arginine I 25.00 M 1 11.9 10.5824 1.75 61.61 67.67 79.00 5.45 66.92 5.32

6006 Arginine I 29.00 M 1 12.9 11.2288 1.77 61.81 67.67 104.00 6.38 66.61 4.80

6009 Arginine I 24.00 M 1 11.1 9.3890 2.04 62.85 68.06 . 7.61 63.96 1.11

6012 Arginine I 30.00 M 1 8.0 7.9967 1.85 . 67.39 32.00 8.56 64.78 .

6015 Arginine I 21.00 M 1 9.0 7.8276 2.24 64.08 70.30 45.00 7.80 69.85 5.77

6018 L-dopa 39.60 M 1 7.3 6.2066 2.37 . 67.20 81.00 12.05 68.17 .

6020 Arginine I 21.40 M 1 12.4 10.4631 1.81 63.88 64.97 62.00 6.17 67.55 3.67

6029 . F 1 9.3 7.1645 2.00 57.14 64.74 92.00 7.39 63.45 6.32

6034 Arginine I 34.00 F 1 9.8 8.1024 2.83 61.72 65.31 269.00 6.34 64.62 2.90

6036 L-dopa 28.00 F 1 5.4 . 1.85 . 62.99 184.00 11.11 62.87 .

7001 Clonidine 30.00 M 1 12.5 11.7559 0.97 62.94 66.11 111.00 5.52 66.11 3.16

7004 . M 1 11.6 11.0498 . 62.45 64.64 147.00 6.04 64.86 2.41

7007 . M 1 11.5 11.0498 1.26 62.93 65.91 146.00 4.96 64.16 1.22

7013 . F 1 9.1 7.8260 0.36 54.72 58.50 85.00 5.00 54.68 -0.04

7016 . F 1 8.6 6.7992 1.32 60.40 59.96 142.00 5.92 59.16 -1.24

 

 

 

Final ht minus Predicted ht (inches)

Mean 2.81

Median 2.90

 

 

 

 

Study GDCH Final Height Population Data

-------------------------------------- THERAPY=Humatrope --------------------------------------

s d

P t b l i

A i s t a a f

T m t b a s s Y f f

I t i l b b r e t E i h

E e m s t A a l g i i A n t

N s g e a G g h p e g g R h p

T t h x n E e v h t f f S t h

1003 Arginine 13.30 M 3 14.2 12.5000 3.12 63.07 73.87 226.60 362 4.85 64.52 1.45

1006 Arginine 30.00 M 1 10.0 6.0000 2.18 61.58 64.94 244.00 399 4.55 63.83 2.24

1008 Arginine 33.30 M 2 13.6 13.0000 3.28 62.17 63.46 268.00 262 3.51 60.40 -1.77

1052 Arginine 25.50 M 2 11.1 11.0000 2.61 62.87 66.61 124.96 386 5.57 63.93 1.06

1053 Clonidine 18.00 M 2 14.4 10.0000 3.19 61.42 65.87 176.00 179 4.63 63.22 1.80

1055 L dopa 31.00 M 2 12.8 8.8333 1.85 62.70 64.27 297.00 581 4.59 62.77 0.07

1056 Arginine 10.00 M 2 12.1 11.5000 1.47 62.91 60.70 118.36 296 4.40 61.34 -1.57

1059 Arg+Ldopa 19.20 M 1 10.6 8.0000 1.47 64.39 66.51 70.13 214 9.08 64.96 0.57

1062 Arginine 21.90 M 1 11.0 9.0000 1.68 58.34 62.17 318.80 620 5.00 58.70 0.36

1063 Arginine 12.80 M 1 11.4 10.0000 1.44 61.62 63.41 173.80 499 5.52 63.08 1.47

1064 Clonidine 21.00 M 2 13.3 11.5000 1.54 62.84 64.86 309.10 . 0.50 63.05 0.21

1069 Arginine 9.20 M 2 12.3 11.0000 1.23 62.38 65.23 . 232 4.56 61.34 -1.04

1070 Arginine 13.00 M 2 14.7 9.0000 2.75 63.04 65.50 228.67 357 4.06 61.49 -1.54

1102 L dopa 12.00 M 2 14.6 11.0000 1.80 65.79 62.73 180.40 387 5.03 65.67 -0.12

1103 Arginine 10.00 M 2 15.1 13.0000 2.07 66.51 64.94 143.53 218 3.28 66.54 0.04

1106 L dopa 23.50 M 2 12.3 9.0000 2.02 64.05 68.76 126.00 196 6.04 68.36 4.31

1109 Arginine 11.70 M 1 14.8 12.5000 1.93 65.75 68.41 125.00 181 3.58 67.41 1.66

1153 Arginine 7.90 F 1 11.4 10.5000 1.18 54.90 58.21 265.00 535 4.04 57.47 2.57

1154 Arginine 8.55 F 2 11.2 12.0000 3.02 56.60 62.35 258.67 595 2.03 57.54 0.94

1203 L dopa 11.40 F 1 10.3 8.0000 1.81 58.09 61.43 99.00 312 6.46 61.11 3.01

1251 Arginine 17.60 F 1 11.5 10.0000 0.75 59.71 63.75 307.00 424 5.44 61.49 1.78

1651 Arginine 13.10 M 1 12.0 12.5000 2.25 63.19 64.84 118.80 375 4.89 64.19 1.01

 

 

 

Final ht minus Predicted ht (inches)

Mean 0.84

Median 0.97

 

Study GDCH Final Height Population Data

--------------------------------------- THERAPY=Placebo ---------------------------------------

s d

P t b l i

A i s t a a f

T m t b a s s Y f f

I t i l b b r e t E i h

E e m s t A a l g i i A n t

N s g e a G g h p e g g R h p

T t h x n E e v h t f f S t h

1005 Arginine 10.00 M 2 11.5 . 1.17 59.09 61.97 104.00 152 5.33 59.12 0.03

1051 Arginine 11.90 M 2 12.9 10.0000 3.12 63.22 65.05 268.84 309 4.10 63.27 0.05

1054 L dopa 13.00 M 3 14.4 12.0000 3.77 64.12 63.73 374.00 397 4.11 61.94 -2.17

1058 L dopa 8.20 M 2 12.4 9.0000 2.07 63.36 65.38 120.80 184 6.14 64.33 0.96

1060 L dopa 16.00 M 3 13.3 10.0000 3.61 64.94 . 362.27 430 3.16 62.46 -2.47

1061 Arginine 13.80 M 1 12.3 10.0000 1.88 62.92 65.60 196.10 423 5.05 62.47 -0.45

1065 Exercise 57.00 M 2 15.2 12.5000 2.13 63.16 68.21 253.00 289 2.86 61.00 -2.16

1104 Arginine 10.20 M 2 12.5 . 1.79 . 66.43 181.00 . 0.11 64.15 .

1151 Arginine 25.60 F 2 12.8 10.0000 1.84 55.98 57.78 178.20 532 4.03 57.00 1.01

1204 Arginine 13.50 F 2 12.5 11.0000 1.80 59.22 59.87 304.67 496 3.93 59.21 -0.01

1601 Arginine 14.00 M 1 12.1 11.5000 0.99 57.97 66.73 109.27 396 5.87 60.56 2.5

 

 

Final ht minus Predicted ht (inches)

Mean -0.26

Median 0.01

Study GDCH Final Height Population Data / IGF-1 Normal Limits for first IGF value

PATIENT THERAPY LOLIM HILIM

1003 Humatrope 220.00 616.00

1008 Humatrope 220.00 616.00

1052 Humatrope 180.00 440.00

1053 Humatrope 220.00 616.00

1055 Humatrope 220.00 616.00

1056 Humatrope 180.00 440.00

1059 Humatrope 136.00 308.00

1062 Humatrope 180.00 440.00

1063 Humatrope 180.00 440.00

1069 Humatrope 180.00 440.00

1070 Humatrope 220.00 616.00

1102 Humatrope 220.00 616.00

1103 Humatrope 200.00 836.00

1106 Humatrope 180.00 440.00

1109 Humatrope 220.00 616.00

1154 Humatrope 191.00 462.00

1203 Humatrope 123.00 330.00

1251 Humatrope 191.00 462.00

1651 Humatrope 180.00 440.00

1005 Placebo 180.00 440.00

1051 Placebo 180.00 440.00

1058 Placebo 180.00 440.00

1060 Placebo 220.00 616.00

1061 Placebo 180.00 440.00

1065 Placebo 286.00 627.00

1151 Placebo 191.00 462.00

1601 Placebo 180.00 440.00

Study GDCH Final Height Population Data / IGF-1 Normal Limits for last IGF-1 value

PATIENT THERAPY LOLIM HILIM

1003 Humatrope 200.00 836.00

1008 Humatrope 286.00 627.00

1052 Humatrope 200.00 836.00

1053 Humatrope 339.00 418.00

1055 Humatrope 220.00 616.00

1056 Humatrope 200.00 836.00

1059 Humatrope 339.00 418.00

1062 Humatrope 220.00 616.00

1063 Humatrope 220.00 616.00

1069 Humatrope 180.00 440.00

1070 Humatrope 220.00 616.00

1102 Humatrope 200.00 836.00

1103 Humatrope 286.00 627.00

1106 Humatrope 286.00 627.00

1109 Humatrope 286.00 627.00

1154 Humatrope 191.00 462.00

1203 Humatrope 286.00 660.00

1251 Humatrope 191.00 462.00

1651 Humatrope 220.00 616.00

1005 Placebo 200.00 836.00

1051 Placebo 220.00 616.00

1058 Placebo 286.00 627.00

1060 Placebo 220.00 616.00

1061 Placebo 220.00 616.00

1065 Placebo 286.00 627.00

1151 Placebo 286.00 660.00

1601 Placebo 220.00 616.00